Antifungal activity of propolis against Candida spp

Fungal infections caused by Candida species remain a major clinical and pharmacological challenge, ranging from superficial mucocutaneous disease to invasive infections associated with considerable morbidity. Vulvovaginal candidiasis is among the most common manifestations and is frequently recurrent. Increasing antifungal resistance has reduced the effectiveness of azoles and other standard therapies, highlighting the need for alternative or complementary treatment strategies. This systematic review aimed to synthesize recent evidence on the antifungal activity of propolis and its mechanisms of action against Candida species. A systematic literature search was conducted in Scopus and ScienceDirect in accordance with PRISMA 2020 guidelines. Original English-language studies published between 2015 and 2025 were included. Evidence from in vitro, in vivo, and clinical studies evaluating antifungal activity, biofilm inhibition, and mechanistic outcomes was synthesized. The selection criteria for Candida isolates in the reviewed studies were categorized into two primary groups to ensure both scientific rigor and clinical relevance. Firstly, standard reference strains C. albicans ATCC 90028, MTCC 227 were utilized to provide a baseline for antifungal efficacy and to maintain quality control during susceptibility testing Secondly, clinical isolates were sourced from patients with diverse pathological conditions, such as acute vulvovaginal candidiasis (VVC), recurrent VVC (RVVC), and device-associated infections (e.g., from IUD users. This inclusion of real-world strains is critical as clinical isolates often exhibit high biofilm-forming potential and multidrug resistance, which standard strains may not fully represent. A total of 62 studies met the inclusion criteria. Propolis showed broad-spectrum antifungal activity against Candida albicans and non-albicans species, with inhibitory doses varying by geographic origin and chemical composition. Higher potency was reported for Brazilian, Nigerian, and Moroccan propolis, largely linked to phenolic acids, flavonoids, and benzophenones. Reported mechanisms of action included disruption of fungal cell membranes and cell walls, inhibition and eradication of biofilms, suppression of morphogenetic transitions and virulence-related gene expression, synergistic interactions with conventional antifungal agents, and modulation of host immune responses. Despite the limited number of in vivo and clinical investigations, current findings suggest that propolis can produce therapeutic effects similar to conventional antifungal agents, without raising significant safety concerns.